SWITCHING BETWEEN CYCLOSPORINE FORMULATIONS - WHAT ARE THE RISKS

The introduction of cyclosporin, refinement in surgical techniques and improvement in allograft preservation have all led to an improvement in graft and ultimately patient survival. Cyclosporin is a lipophilic cyclic polypeptide produced by Trichoderma, a fungus isolated from Nor wegian soil. Cyclosporin is a potent, selective and powerful immunosup pressive agent possessing a narrow therapeutic window. Substitution am ong different formulations of cyclosporin for economic reasons, withou t close monitoring of pharmacokinetics and pharmacodynamics, can induc e undesirable toxic effects. A number of recent reports, largely anecd otal, of adverse drug reactions and acute cellular rejection after con version from the standard formulation to the microemulsion formulation of cyclosporin have created uncertainty over the therapeutic equivale ncy of these agents. This leading article reviews the pharmacology, ph armacokinetics and adverse drug reactions of cyclosporin as well as th e potential risks associated with switching between cyclosporin formul ations in stable renal transplant recipients. Caution should be employ ed when switching between cyclosporin formulations. Since data are lim ited, long-term prospective studies are necessary to delineate the rol e of high peak concentrations obtained from the microemulsion formulat ion in relation to cyclosporin-induced chronic nephropathy. The signif icance of the reduction in pharmacokinetic variability with use of the microemulsion formulation in terms of graft and patient survival rema ins unclear.